Possible Interaction: Gamma-Aminobutyric Acid and Thiopental

“Corresponding experiments revealed (a) that the duration of recurrent inhibition was more prolonged by thiopental in young compared to elderly animals and (b) that thiopental enhanced the γ-amino-butyric acid (GABA) release from pre-synaptic terminals in an age-dependent manner.”

“At a clinically relevant concentration (30 &mgr;M), thiopental markedly enhanced the peak amplitude of a subsaturating GABA-induced current ( IGABA ) but not that of a saturating GABA-induced cur-rent.”

“Furthermore, thiopental prolonged the time constants of both desensitization and deactivation of IGABA.”

“In addition, the degree of serum thiobarbituric acid (TBA)-reactive substance level was significantly lower in the rats treated with 100 mg GABA , and the degree of TBA-reactive substance in the liver and kidney was reduced by GABA in a dose-dependent manner.”

“Halothane and isoflurane, but not thiamylal or thiopental , significantly inhibited uptake by COS cell systems of GABA , dopamine and glutamic acid in a concentration-dependent manner within clinically relevant ranges for anesthesia induced by these agents.”

“The model indicated that GABA enhanced the affinity of thiopental 3.0-fold, propofol 5.0-fold, the neuroactive steroids Org 20599 3.5-fold and Org 20549 13-fold.”

“…,thiopental , and … of3 H‐GABA uptake: IC50 = 4.6 plus/minus 0.3 x 105 M, 5.8 plus/minus 0.3 x 10 sup ‐5 M, … sup ‐3 M, and 4.9 plus/minus 0.5 x 10 sup ‐4 M for propofol, etomidate, thiopental, and ketamine, respectively.”

“These data corroborate the importance of a prolongation of gamma-aminobutyric acid A-mediated inhibition to the mechanism of actions of etomidate, thiopental , and Saffan at relevant exposure concentrations in vivo.”

“ Thiopental intensified the depression produced by GABA.”

“4 Thiopentone , pentobarbitone, methohexitone and hydroxydione inhibited K+‐stimulated GABA and D‐aspartate release.”

“10 days) rats, less enhancement of thiopental on GABA inhibition of the field potentials was observed.”

“In slice preparations, thiopental at a concentration of 10(?5) M enhanced the GABA (1?5 x 10(?4)M) inhibition of the field potentials evoked in pyramidal neurons by stratum radiatum stimulation.”